2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.02F.01 Berberine and Osimertinib Inhibit Progression of EGFR-TKI Primary and Acquired Resistant NSCLC Cells by a Multimodal Intervention

EP.02F.01 Berberine and Osimertinib Inhibit Progression of EGFR-TKI Primary and Acquired Resistant NSCLC Cells by a Multimodal Intervention

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The study investigates the combined effects of berberine (BBR), a natural anti-cancer compound, and osimertinib (Osi), a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), on non-small cell lung cancer (NSCLC) cells. Addressing the challenge of primary and acquired resistance to EGFR-TKIs in lung cancer treatments, this research explores whether the two substances can work synergistically to enhance therapeutic outcomes.<br /><br />Methods included treating NSCLC cells with BBR and Osi, then examining cell cycle alterations and apoptosis using flow cytometry. Metastasis-related phenotypes were evaluated through various assays including transwell migration, adhesion, angiogenesis, and cytoskeletal staining. Western blot analysis was used to assess changes in proteins associated with the cell cycle, apoptosis, and metastasis. In vivo experiments were performed using tumor xenografts in mice and lung cancer organoids.<br /><br />Results demonstrated that BBR, both alone and in combination with Osi, effectively inhibited NSCLC progression, especially in cells resistant to EGFR-TKIs. This was achieved through arresting the cell cycle at G0/G1 or G2/M phases, enhancing apoptosis, and reducing metastasis. The combination of BBR and Osi significantly decreased tumor migration, invasion, cell adhesion, and the formation of vascular-like structures, while altering the morphology of microtubules and microfilaments. It also inhibited the growth of NSCLC cells resistant to EGFR-TKIs in vitro and reduced tumor growth in xenograft models and organoids.<br /><br />The conclusion emphasizes the potential of combining BBR and Osi as a promising therapeutic strategy for NSCLC by suppressing cell proliferation, inducing cell cycle arrest, enhancing apoptosis, and preventing metastasis. These findings underline the importance of multimodal intervention strategies in overcoming drug resistance in lung cancer treatment.

Asset Subtitle

Zixuan Hu

Meta Tag

Speaker Zixuan Hu

Topic Tumor Biology – Preclinical Biology

Keywords

berberine

osimertinib

non-small cell lung cancer

EGFR-TKI resistance

synergistic treatment

cell cycle arrest

apoptosis

metastasis inhibition

tumor xenografts

lung cancer organoids